Reprod (Q & A) 1

Q. List different Male Sexual Organs A) Primary reproductive organs: The testis:- composed of coiled seminiferous tubules. B) 2ry sex organs: 1- The epididymis. 2- The vas deferens. 3- The seminal vesicle empties into ampulla. 4- The ejaculatory ducts. 5- The urethra is the last connection link between testis & exterior. 6- The bulbouretheral glands located near origin of urethra.

Q. Summarize functions of male sex organs Organ Structure Function

Testes

formed of seminiferous tubules separated by interstitial cells.

production of sperm (seminiferous tubules/FSH); secretion of testosterone (interstitial cells, LH)

Epididymis

tightly coiled tubule superior to testes; leads to vas deferens

- site of sperm maturation. - site of acquiring motility. - storage of epididymis.

Vas Deferens

muscular tube leading from epididymis.

- storage of sperms. - movement of sperm

Seminal Vesicle

sac-like structure attached to vas deferens

- dilute thick mass of sperm that make them mobile. - provide more than 50% of semen. - contain fibrinogen that helps to clot semen in vagina immediately after ejaculation. - contains prostaglandins: * reacting with cervical mucus to help rapid passage of sperm into uterus. * inducing reverse contraction in the uterus & fallopian tubes to move sperm toward ovary. - addition of fructose (energy source) to sperm/semen

Prostate Gland

sponge-like structure below bladder and surrounding urethra

- addition of milky alkaline fluid to semen to neutralize acidity of fluid of vas and vaginal secretion so increase sperm motility & fertility. - contain Ca, citrate and phosphate ions. - contain clotting enzymes & fibrinolysin: * clotting enzymes: act on fibrinogen to clot semen after ejaculation. * fibrinolysin dissolves semen after few minutes.

Bulbourethral Gls

two structures below prostate Secrete mucus for lubrication of sexual intercourse.

Penis

vascular columns fill with blood causing erection

is held in female vagina during intercourse for transfer of sperm

Scrotum pouch of skin and fat allow cooler temperature to insure sperm production

Reprod (Q & A) 2

Q. Describe Functions of male reproductive system 1- The testis The testis is composed of 2 parts:

I- The seminiferous tubules: They are 900 coiled tubes in which the sperms are formed (spermatogenesis). They contain sertoli cells that extend the whole thickness from the basement membrane to the lumen.

II- Interstitial cells of Leydig (Leydig cells): These cells are large cells that are situated in the connective tissue between the seminiferous tubules. These cells secrete androgens chiefly testosterone.

2- Epididymis * Receive the sperm & Sertoli cell secretion. * Sperms are stored, mature & gain motility. * Concentrate the sperms.

3- Vas deferens * Carries semen from epididymis to ejaculatory ducts. * Stores sperms until ejaculated.

4- Seminal vesicles: produce about 60% of the semen * Secrete a mucoid material that contain fructose, citric acid, other nutrient and large quantities of prostaglandins and fibrinogen * Empties its content into the ejaculatory duct during the process of emission * Fructose and other substances are of considerable nutrient value for the ejaculated sperm. * Secrete fibrinogen for seminal clotting. * Prostaglandins are believed to aid fertilization by: reacting with cervical mucus to make it more receptive to sperm movement possibly causing reverse peristaltic contraction of the uterus and fallopian tubes to move the sperm towards the ovaries

5- Prostate Secretes about one third of the semen volume. It secretes a milky, slightly acidic fluid containing citrate, acid phosphatase and several proteolytic enzymes. These enzymes are probably involved in breaking down the mucus plug in the cervix. They also appear to contribute to the motility and viability of the sperm

6- Bulouretheral glands * Produce mucus for lubrication and is believed to neutralize traces of acidic urine in the urethra.

Reprod (Q & A) 3

Q. Enumerate different functions of Sertoli cells Large cells extend from basement membrane of seminiferous tubule to its lumen. Their development is stimulated by FSH. Functions of Sertoli cells 1- Tight junctions between Sertoli cells form blood testis barrier:

* Maintain critical composition of tubular fluid for sperm maturation. * It also prevents harmful substances in blood from reaching the lumen & protects sperms. * Prevents antigenic products of germ cell division from entering the blood so prevent the formation of antibodies.

2- Nutritive function:

Sertoli cells secrete fluid to provide nutrients for newly formed sperms. 3-They play a special role in converting spermatid into sperm (spermiogenesis).

They secrete enzymes which remove cytoplasm from spermatid & play a role in shaping the head & tail of sperm.

4- Endocrine function:

*They produce Androgen-binding protein that binds both testosterone & estrogen making them available for maturing sperm. ABP is found at high concentrations in the human testes and epididymis. It serves as a carrier of testosterone in Sertoli cells, as a storage protein for androgens in the seminiferous tubules, and as a carrier of testosterone from the testes to the epididymis. *Mullerian inhibitory factor (MIF): inhibit formation of fallopian tubes from mullerian ducts in the male fetus. * Estradiol: has a stimulatory factor for spermatogenesis. * Inhibin: has inhibitory effect on A.P gland to prevent FSH oversecretion.

Reprod (Q & A) 4

Q. Discuss Endocrine functions of the testis -The testes secrete several male hormones called androgens (Any steroid hormone that has masculinizing effect). -Androgens include testosterone, dihydrotestosterone & androstenedione. -Testosterone is the most abundant androgen. Much of testosterone is converted by the enzyme 5α-reductase into the more active dihydrotestosterone in target tissues. -Testosterone is secreted from Leydig cells which lie between seminiferous tubule. -Testosterone is transported in blood bound to plasma protein.

Functions of testosterone I- During fetal development (intrauterine) Testosterone is responsible for: 1- The development of male sex organs. 2- Suppressing the formation of female genital organs. 3- Descending of the testis into the scrotum during the last 2 months of pregnancy. II- On reproductive system: 1- Genitalia increase in size & start functional manifestation. 2- essential for vitality of germinal epithelium. 3- needed for maturation of spermatozoa. 4- negative feedback control on gonadotrpin secretion. III- on secondary sexual characteristics Essential for Development of secondary sexual characteristics:- * Development of beard & moustache. * Growth of hair over pubis, chest & other regions. * Receding hair line on top of head. * The voice become deep and low pitched. * Thickness of skin over body & increase secretion of sebaceous glands. (++ liability for acne). * Mental changes: aggressive behavior. * develops libido and maintain it after pubery. * broad shoulder and narrow pelvis. IV- Non reproductive effects 1- Protein anabolic effect. 2- Bone growth at puberty & early union of epiphysis with the shaft. 3- Increase RBCs number. 4- Increase circulating LDL cholesterol & decrease HDL cholesterol. 5- increase the reabsorption of sodium in the distal tubules of the kidneys. 6- Increase basal metabolic rate. Mechanism of action of testosterone Testosterone is converted in the cell into DHT which binds to cytoplasmic receptor protein. The combination migrates to nucleus and induces DNA-RNA transcription process followed by increase cellular protein.

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Q. Describe Regulation of Testosterone Secretion 1- Hypothalamic regulation: The hypothalamus secretes GnRH into the hypothalamic-hypophyseal portal vessels. GnRH stimulates the secretion of FSH and LH from the anterior pituitary. 2- Anterior pituitary regulation: It secretes FSH and LH. FSH acts on the sertoli cells to maintain spermatogenesis. LH acts on Leydig cells to promote testosterone synthesis. 3- Negative feedback: a- Testosterone inhibits the secretion of LH by inhibiting the release of GnRH from the hypothalamus and by inhibiting the secretion of LH directly from the anterior pituitary. b- Sertoli cells secrete inhibin which inhibits the secretion of FSH from the anterior pituitary.

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Q. Describe the structure of The sperm a. The head contains 23 chromosomes and is covered by an acrosome, contains enzymes to help penetrate the oocyte. b. The body (mid-piece) * contains many mitochondria needed to produce ATP for energy for the sperm cell to complete its long journey; c. The tail * provides locomotion for the sperm cell. * Maturation of sperm in epididymis. * The newly formed sperms are no motile and cannot fertilize the ovum. *The sperms mature & become able to motile in epididymis. * Storage of sperms

* Small quantity can be stored in epididymis. * Most sperms are stored in vas deferens and ampulla & maintain their fertility for a month.

Q. Describe the process of Spermatogenesis Site: All seminiferous tubules. Start: At average age of 13 years by Gonadotropic hormones & continuing throughout the remainder of life. Takes: about 74 days to form mature sperm from germ cells. Phases: 3 phases One spermatogonium (23 pairs of chromosomes) duplicates its DNA. This gives rise to One primary spermatocyte (23 duplicated pairs of chromosomes) which undergoes meiosis I. This gives rise to Two secondary spermatocytes (each with 23 duplicated chromosomes), which undergo meiosis II. This gives rise to Four spermatids (each with 23 chromosomes). These cells mature into Four sperm cells (each with 23 chromosomes). The sperm cells collect in the lumen of the seminiferous tubule.

Reprod (Q & A) 7

Q. Discuss Factors affecting spermatogenesis A) Endocrine control of spermatogenesis 1. Testosterone, secreted by the Leydig cells located in the interstitium of the testis:

is essential for growth and division of the testicular germinal cells.

needed for mitotic and meiotic divisions.

help maturation of spermatids into spermatozoa.

2. Luteinizing hormone, secreted by the anterior pituitary gland,

stimulates the Leydig cells to secrete testosterone.

3. Follicle-stimulating hormone, secreted by the anterior pituitary gland,

Maintain spermatogenic epithelium.

stimulates the Sertoli cells. (spermatid maturation & ABP production).

help maturation of spermatids into spermatozoa.

4. Estrogens, formed from testosterone by the Sertoli cell when they are stimulated by FSH

probably also essential for spermiogenesis

Sertoli cells also secrete an androgen-binding protein that binds both testosterone and estrogen and carries

them into the lumen of the seminiferous tubules to make them available for the maturing sperm

5. Growth hormone (as well as most of the other body hormones) is necessary for controlling background

metabolic functions of the testes.

Growth hormone specifically promotes early division of the spermatogonia.

1- FSH stimulates Sertoli cells which help spermiogenesis. 2- LH stimulates Leydig cells to secrete testosterone. 3- Testosterone secreted from Leydig cells & is essential for growth & division of germinal cells. 4- Estrogen formed from testosterone by Sertoli cells. It is essential for spermiogenesis. 5- Growth hormone necessary for controlling metabolic function of testis.

B) Temperature: suitable temp (32-35C). * Increasing the temperature of the testes can prevent spermatogenesis by causing degeneration of most cells of the seminiferous tubules besides the spermatogonia. * The testes are located in the scrotum is to maintain the temperature of these glands below the internal temperature of the body, although usually only about 2-4 °C below the internal temperature. Testes are kept cool by: * Thin scrotal skin that contain many sweat glands. * heat exchange in a countercurrent fasion between the spermatic arteries and veins. * absence of subcutaneous fat * On cold days, the musculature of the scrotum to contract, pulling the testes close to the body. * On hot days, the musculature of the scrotum to relax, pulling the testes away from the body.

Reprod (Q & A) 8

Cryptrochidism Def: Failure of a testis to descend from the abdomen into the scrotum. Effects: The tubular epithelium becomes degenerate, leaving only the interstitial structures of the testis, consequently, causing sterility. Management: Cryptrochdism can be treated by: gonadotrophic hormones and surgical correction of the defect. C) Balanced diet: - protein: - Vitamin A: deficiency of vit A leading to keratinization & atrophy of germinal epithelium. - Vitamin B12: needed for metabolic processes inside the testis. - Vitamin C: deficiency of vit C leading to decreased testosterone secretion. - Vitamin E: deficiency of vit E leading to degeneration of germinal epithelium. E) Extrinsic factors: - Exposure to excess radiations, toxins or chemicals may cause damage of testis. - Exposure to some infectious agents: as mumps and typhus may affect the process.

Q. Describe role of male & female during sexual act Stages of male sexual act The male sexual act results from reflex mechanisms integrated in the sacral & lumbar spinal cord. It is initiated by psychic & sexual stimulation.

Erection; stiffness of penis due to vascular congestion Erection is caused by parasympathetic impulses that pass from sacral portion of spinal cord through pelvic nerve to penis. The fibers secrete NO; a vasodilator. This increases blood flow to penis.

Parasympathetic stimulation (S2,3,4) dilation of arterioles of penis Engorgement with blood compresses venous drainage penis cavities remain engorged with blood

Ejaculation; function of sympathetic nerves Ejaculation is a spinal reflex brought about by sympathetic nerves (arise from L1&2). Contraction ejaculatory duct & seminal vesicles causes emission of semen into urethra, followed by expulsion of semen to outside. The entire period of ejaculation is called sexual orgasm.

Sensory impulses reach critical level sympathetic activation of testes tubules reproductive ducts/glands contract peristaltically bladder sphincter muscle constricts (no urine) sperm moves into the urethra bulbospongiosus muscles contract to expel semen

Female Sexual Response Sexual excitement is initiated by similar stimuli, from thought to sight, smell and touch. It is accompanied by engorgement of the clitoris, vaginal mucosa and breasts with blood; erection of the nipples and increased secretory activity of the vestibular glands that lubricate the vestibule and facilitate entry of the penis. The final phase of the female sexual response, orgasm, is not accompanied by ejaculation although it does give rise to muscle spasm and uterine contractions. This is not associated with ovulation and is not required for conception in humans.

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Q. Describe the manifestations of Hypogonadism Def: decrease in testosterone secretion.

Types: A) primary B) secondary

- due to undescent of testes, loss of testes or a person born without functional testes. - Secretion of GnRH, FSH & LH increased.

- Due to disorders of hypothalamus or anterior pituitary - Secretion of GnRH, FSH & LH increased.

Manifestations: I- If it occurs before puberty 1- Infantile primary & secondary sexual characteristics. 2- The voice is a child type. 3- The normal masculine hair distribution on body does not occur. 4- The height of adult man is greater than that of a normal man. 5- The muscles are weak. II- If it occurs after puberty 1- Some male secondary characteristics revert to those of child type. 2- Sexual organs regress in size. 3- Loss of masculine hair production. 4- Loss of musculature and the bone. 5- Decreased sexual desire.

Q. Describe Semen It contains fibrinogen (from seminal vesicles) that cause semen to coagulate; fibrinotrypsin (from prostate) that causes the clot to dissolve. Normal sperm count is 100 million/ml. Sperms can live for weeks in male genital tract. Once ejaculated their life span is 24-48 h. at body temperature. At lowered temperature semen can be stored for several weeks and when frozen, sperms can live for years.

Sources: 60%: fluid from seminal vesicles., 10%: sperms from vas., 30%: fluid from prostate. - mucous from bulbourethral glands.

pH: 7.5

Consistency: Milky due to prostatic fluid. Mucoid due to seminal vesicles & mucous glands.

Volume: About 3-5 ml is ejaculated each time.

Contents: a) spermatozoa: 100million/ml. less than 20% abnormal forms. Motile, more than 60% motile. b) Secretions: - Testicular: hyalourindase (dissolve cervical mucous). Buffers.

- Prostatic: cholesterol, fibrinolysins (liquefies seminal fluid after ejaculation). - Seminal vesicles: Fructose, PGs (++uterine motility).

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Q. List functions of FEMALE REPRODUCTIVE ORGANS

Organ Structure Function Ovary

solid, ovoid structures on posterior pelvic cavity; cortex of ovarian follicles

production of secondary oocytes for fertilization; production of estrogen for development of secondary sex organs; production of progesterone to prepare endometrium for implantation

Fallopian Tube

tubes that pass medially from ovaries to uterus; lined with cilia, expanded ends (fimbriae) over ovary

site of fertilization; transportation of fertilized egg to uterus

Uterus muscular (smooth) organ that houses developing embryo, fetus; 3 layers

houses developing embryo/fetus

Cervix lower one-third of uterus Pap smear location

Vagina passageway from cervix to outside birth canal; houses erect penis during intercourse

Labia external reproductive organs protect underlying organs

Clitoris small projection at anterior end of labia; two columns of vascular tissue

female excitatory organ

Q. Describe the process of Oogenesis a. all potential gametes produced before birth b. Meiotic divisions unequal, leading to the formation of polar bodies (eventually destroyed) c. puberty releases the "arrested state" of primary oocytes, leading to ovulation d. Meiosis II does not occur until fertilization of the secondary oocyte by mature sperm e. ovulation and reproduction naturally end during menopause.

fetus: oogonia (diploid stem cells) primary oocytes / follicle cells (prim. follicle) primary oocyte arrested in Prophase I (ovary cortex) childhood: about 700,000 primary oocytes ready to go puberty primary oocyte (primordial follicle) completes Meiosis I to produce 2 haploid cells secondary oocyte + first polar body ovulation: secondary oocyte released by ovary fertilization: sperm penetrates secondary oocyte completion of Meiosis II to produce 1 very large haploid OVUM + polar body

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Q. Describe changes that occur during Ovarian cycle Changes which occur in the ovaries during each cycle can be divided into:-

1- Follicular phase. 2- The ovulatory process.

3- The luteal phase. 1- The follicular phase

1- Due to increased levels of FSH secreted from the anterior pituitary 10-15 primordial follicles start growing. 2- follicular cells: Granulosa cells secrete local estrogen. The thecal cells secrete systemic estrogen 3- Increased FSH will lead to multiplication of granulosa and thecal cells, so the follicles increase in size and fluid collects between granulosa cells forming a large cavity filled with fluid called antrum. 4- At 6th day, One of the follicles begins to outgrow all the others (become dominant) and all the rest begin to involute and become atretic. 5- This occurs because the dominant follicle secretes more local estrogen which increase in the number of FSH receptors on granulosa cells thus increasing the stimulatory effect of FSH receptors on this follicle. 6- However the increased estrogen acts on the hypothalamus and pituitary to inhibit the secretion of FSH and LH thus decreases the degree of stimulation of other follicles. 7- The mature follicle is called the graffian follicle. 2- The ovulatory process 1- It occurs 14 days before menses. 2- In the late follicular phase (12-13 days) estrogen levels peak. 3- Very high levels of estrogen act on the anterior pituitary to increase secretion of LH (+ve feedback). This produces LH surge. 4- Also at the same time there is increase in FSH secretion and progesterone starts to be secreted. 5- At day 14, LH surge induces ovulation by increased secretion of digestive enzymes and prostaglandins. This leads to rupture of the follicle with release of the ovum surrounded by several layers of granulosa cells into the peritoneal cavity to be picked by the fimbriated end of the fallopian tube. N.B. Just before ovulation the 1st meiotic division is completed. One of the daughter cells is the 2ry oocyte which receives most of the cytoplasm and the second one is the 1st polar body which is expelled from the nucleus of the oocyte.

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3- The luteal phase After ovulation, LH acts on follicular cells which differentiate into luteal cells and corpus luteum is formed (luetinization). It secretes Estrogen & progesterone (mainly). The rising level of these hormones inhibits the secretion of LH & FSH by –ve feedback effect. Loss of these 2 hormones causes corpus luteum to degenerate (if no pregnancy takes place) and is replaced by C.T & become corpus albicans. Degeneration of Corpus luteum causes E & P levels to decline and remove the –ve feedback effect from PG allowing rise of FSH to stimulate maturation of more follicles for the next cycle.

A. follicular phase B. Ovulation C. luteal phase 1. primordial follicle primary follicle 2. primary follicle secondary follicle 3. ovary cortex forms theca folliculi around granulose theca folliculi & granulosa produce estrogens 4. granulosa form jelly-like zona pellucida 5. fluid-filled space called antrum develops 6. primary follicle now becomes a secondary follicle secondary (vesicular) follicle reaches ovary surface

1. fluid filled antrum increases in size corona radiata begins to separate from wall 2. ovulation - secondary oocyte (surrounded by the corona radiata) bursts from the ovary into the peritoneal cavity (fimbriae pick up!) a.mittelschmerz - pain associated with ovulation

corpus luteum forms from granulosa and thecal cells remaining from the bursting site; it secretes progesterone and some estrogen a. YES pregnancy -> secrete more progesterone b. NO pregnancy -> whole structure will degenerate (no more progesterone).

Q. Describe changes that occur during uterine cycle Can be divided into proliferative, secretory & menstrual phases. The proliferative phase After menstruation, a thin layer of endometrial stroma remains. Under the influence of estrogen, stromal cells proliferate, endometrial glands become long & tortuous. The blood supply of endometrium grows. During this period, the endometrium grows from 3-4 mm in height.

1- Increased estrogen in the 5th day stimulates regeneration and growth of endometrium. 2- Estrogen stimulates growth of endometrial glands.

3- Estrogen stimulates development of endometrial blood vessels. 4- At the end of this phase the endometrium is 3-4 mm in thickness.

The secretory phase It occupies the time from ovulation until menstruation. Progesterone is the dominant hormone. Estrogen causes slight additional cellular proliferation in endometrium. Progesterone causes functional changes in endometrium to prepare it for implantation. The glands increase in tortuosity and acquire secretory activity. The arteries become more prominent & coiled.

1- After ovulation increased progesterone stimulates the secretion of glands which become coiled. 2- It also stimulates development of blood vessels which become coiled.

3- Progesterone stimulates glycogen deposition in the endometrium. 4- The endometrium becomes 6-7 mm in thickness.

Further changes depend on whether implantation has taken place or not:

1- Implantation: if pregnancy occurs, the embryo secrete hCG hormone that maintain corpus luteum & so the secretion of estrogen & progesterone continues. The stromal cells proliferate & differentiate into layers.

Reprod (Q & A) 13

2- Non implantation: In absence of hCG, corpus luteum declines and E & P levels decrease. This result in reduction in endometrial tissue height and more coiling of arteries with secondary ischemia and blanching of endometrium. Menstruation 1- After degeneration of corpus luteum there is marked drop in the level of the ovarian hormones. 2- This leads to prostaglandins release from the endometrium. 3- Prostaglandins cause spasm of blood vessels and ischemia of the endometrium followed by necrosis. 4- This leads to sloughing of the endometrium and beginning of menstrual flow which occurs in the 1st 5 days of the follicular phase and the cycle repeats itself. The superficial endometrial layers are shed. The necrotic tissues are extruded into uterine cavity and initiate uterine contraction to expel the contents. Volume of menstrual blood is 50-70 ml. which is mostly arterial blood with only 25% venous blood. It contains tissue debris, prostaglandins, fibrinolysin (to prevent blood clotting) & large number of leucocytes (for defense of endometrium against infection). The menstrual flow stops in 5-7 days

Reprod (Q & A) 14

Q. Mention Changes in the cervix during the uterine cycle During the proliferative phase, cervical mucous secretion is thin & alkaline. (estrogen effect) After ovulation, the mucus becomes thick & difficult to penetrate. (progesterone effect)

Q. Mention Changes in the vagina during the uterine cycle During proliferative phase, Estrogen causes vaginal epithelium to be cornified & acidic. After ovulation, progesterone increases vaginal secretion.

Q. What is the Anovulatory cycles Ovulation does not occur. This can occur during the first cycles following puberty and prior to menopause where the LH surge is not potent to cause ovulation. Lack of ovulation causes failure of development of corpus L and no secretion of progesterone during 2nd half of the cycle. The cycle is shortened but the rhythm continues.

Q. List important Signs of ovulation 1- Detection of manifestation of secretory phase in an endometrial biopsy. 2- Rise of body temperature 0.3-0.5 oC at mid cycle + lower abdominal pain. 3- Thick cervical mucous in the second half of the cycle. 4- Rise of blood progesterone level & its urinary output.

Q. Mention different effects of Estrogens The main natural estrogens are:- 17β estradiol, estrone & estriol. Estradiole is the most active, while estriol is the least. They are secreted by : Granulosa cells of the ovarian follicles, corpus luteum, placenta & adrenal cortex. 97% of estradiol bound to plasma protein. Estrogen metabolized in liver. Secretion There are 2 peaks, one just before ovulation and other during midluteal phase. After menopause, estrogen secretion declines to low levels. Actions of estrogens At puberty 1- Cellular growth & proliferation of tissues of sex organs (external &internal). They change from those of a child to those of an adult. 2- Development of secondary sexual characteristics:

*Development of breast duct system & fat deposition (smooth appearance). *Deposition of fat in certain parts → characteristic rounded female figure. *Growth of axillary & pubic hair with flat-topped pattern (androgen effect) *Change in body configuration with narrow shoulder & broad hip. *Voice stays high-pitched. *Skin is soft, smooth & more vascular.

On reproduction 1- On ovaries: E facilitates growth of ovarian follicles. 2- On fallopian tubes: E increases the motility & activity of ciliated epithelial cells and so helps fertilization. 3- On uterus: E causes proliferation of endometrium, growth of uterine muscle, increases its contents of contractile protein & sensitizes uterine muscles to oxytocin. It also increases uterine blood flow.

Reprod (Q & A) 15

4- On breast: It is called the growth hormone of breast:- * E stimulates ductal growth.

* E causes pigmentation of areola. * E increases deposition of fat in breast.

5- Feedback regulation of gonadotropin secretion. 6- Increase libido (sexual desire). Other effects 1- Protein anabolic action 2- Increases osteoblastic activity. It causes early union of epiphysis with shafts of long bone. 3- Salt & water retention by the kidney. 4- Plasma cholesterol lowering effect & low incidence of CVS complications. 5- Secretion of angiotensinogen & thyroxin binding globulin. Mechanism of action of estrogens E combines with receptor (α & β) and the complex binds to DNA promoting mRNA formation that direct formation of new protein which modify cell function.

Q. Mention effects of Progesterone Progeaterone is synthesized in corpus luteum by theca lutein cells, in placenta during pregnancy & in adrenal cortex. It is bound to plasma proteins & metabolized in the liver & excreted in urine. The peak of progesterone is during luteal phase. Actions of progesterone. On the uterus 1- Secretory changes in the mucosal lining of fallopian tubes & in estrogen primed endometriem during the luteal phase. These changes are necessary for implantation & occurs in fallopian tubes. 2- An antiestrogenic effect on myometrium making it less excitable & less sensitive to oxytocin. During pregnancy, progesterone inhibits uterine activity (relaxing effect). 3- on fallobian tubes: produces secretory changes for nutrition of the fertilized dividing ovums. 4- on cervix: thick cervical mucus. On breast Progesterone stimulates growth & proliferation of alveolar tissues & lobules. It causes fluid retention in the subcutaneous tissues. On the brain Negative feedback on the pituitary & hypothalamus. Large dose, inhibits LH secretion preventing ovulation. Other effects 1-Thermogenic effect & increase the metabolic rate & increase body temperature 24 h after ovulation. 2- Stimulation of respiratory centre. 3- Mobilization of protein from the mother for the use of the fetus. (mild catabolic effect). 4- It causes natriuresis by blocking the action of aldosterone.

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Q. Describe neuro-endocrine control of ovarian function A) Gonadotropin-releasing hormone: GnRH

- GnRH secreted from hypothalamus in the form of pulses. - Regulate FSH & LH secretion from anterior pituitary. - Frequency of pulses:

* increased by: estrogen that increase LH surge. * decreased by progesterone.

B) Pituitary gonadotropins: 1- FSH:

- Allow follicular maturation. - FSH → act on granulosa cells→++ estrogen. - FSH → ++ LH receptors on granulosa cells. - ++ estrogen & inhibin by the follicle→ -ve feedbackon FSH→--FSH. - Lowest concentration in the 2nd half of luteal phase.

2- LH: - potentiate stimulatory effect of FSH on follicular growth. - responsible for ovulation. - needed for corpous luteum formation. - High Estrogen levels in near ovuulation, increase GnRH receptors → ++ responsiveness of pituitary to GnRH→ ++LH→ LH surge.

Q. Describe Hormonal Interactions During the Ovarian Cycle 1. GnRH, LH, FSH and their Role in Estrogen Level

a. increasing release of GnRH from hypothalamus increased release of FSH and LH from ant. Pituitary FSH stimulates growth/division of follicle cells LH stimulates development of thecal cells LH stimulates thecal cells to produce androgens FSH stimulates granulosa to convert to estrogens b. temporary NEGATIVE FEEDBACK - these low levels of estrogens briefly inhibits more release of FSH and LH (although it is still being produced and stored!) c. temporary POSITIVE FEEDBACK - these low levels of estrogens briefly enhance FSH stimulation of granulosa

2. Higher Estrogen Leads to Actions of LH a. estrogen levels eventually get higher and higher b. suddenly, high estrogen creates POSITIVE FEEDBACK to brain increasing GnRH, FSH, LH levels c. LH and FSH levels rise very quickly (MIDCYCLE) d. high LH level increases fluid level in antrum, and rupture/release of the secondary oocyte e. estrogen level drops immediately after ovulation, but soon begins to rise again f. LH stimulates "corpus luteum" to secrete progesterone to prepare the endometrium for implantation and pregnancy

3. Continuation Depends on Corpus Luteum and Progesterone

a. progesterone and estrogen levels rise, leading to a negative feedback on LH and FSH. b. LH levels decline, corpus luteum starts to degenerate, and less progesterone released Pregnancy placenta releases Human Chorionic Gonadotropin

(maintaining progesterone levels for pregnancy)

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Q. List different methods of Contraception Oral combined contraception pill

Steroid pill Intra uterine contraceptive device IUCD

Rhythm method IUCD Intrauterine contraceptive device Made of copper Provides low grade chronic inflammation with WBCs destroying sperm Cytotoxic to pre and post implantation (i.e. can be used post coital) Copper is also spermatotoxic Steroid Pill General principal is to prevent ovulation by negative feedback of progesterone on the pituitary and hypothalamus. Progesterone also affects the female genital tract by by thickening cervical mucus. So suppressing sperm penetration. A maximal contraceptive effect and complete continuous amenorrhoea is provided by a high dose of both oestrogen and progesterone. Rhythm method intercourse is avoided 3 days before ovulation, the day of ovulation & 3 days after the expected day of ovulation.

Q. Discuss Puberty -The cause of onset of puberty (8-12years) is maturation process in brain that causes hypothalamus to begin secreting GnRH, due to decrease in the secretion of melatonin (melatonin is an antigonadotropic effect).

Delayed puberty Precocious puberty True pseudo Menarchae failed to occur by the age of 17

or testicular development by the age of 20 years. Causes: 1. chromosomal abnormalities. 2. gonadal dysgenesis. 3. hypopituitrism.

Early gonadotropin secretion Causes: Hypoth. Diseases Pineal tumours. Constitutional.

Early development of 2ry sex character without gametogenesis. Abnormal high levels of estrogen in immature female or androgen in male.

Q. Discuss what is meant by menopause It describes the last period or final cessation of menstruation. It usually occurs in the late 40s to early 50s. Women’s reproduction abilities decline over 2-3 y before As women approaches menopause, the ovaries become depleted of oocytes & become small and consists of fibrous tissue with no follicles. The circulating estrogens fall to very low level and FSH & LH increased. 1- Vasomotor symptoms Hot flushes are sensation of warmth on trunk & face accompanied by sweating & palpitation. 2- Emotional & psychological problems.

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Q. Describe mechanism of Fertilization For fertilization to occur, a viable sperm must meet a viable secondary oocyte. Sperm live for only 48 to 72 hours after ejaculation. The secondary oocyte lives for only 12 to 24 hours after ovulation unless fertilization occurs. Consequently, for fertilization to occur, coitus must occur no more than 72 hours before ovulation and no later than 24 hours after ovulation.

The penetration of the oocyte by sperm normally occurs soon after ovulation. After ejaculation, few sperms reach the outer 1/3 of fallopian tube aided by contraction of uterus & fallopian tube. The ovum is helped to descend down the tube by action of cilia which beat toward uterus. N.B. The changes in the cervical mucus associated with the production of estrogens during the proliferative phase of the uterine cycle make it easier for sperm to penetrate the cervix. The sperms undergo physiological changes during their course in female genital tract i.e. capacitation & acrosome reaction.

Capacitation: sperms develop capacity of fertilization after a few hours in female genital tract. It is due to changes in plasma membrane by enzymes located in acrosome region of the sperm. Acrosome reaction: Sperms undergo structural changes which end by loss of acrosomal cap leaving the inner acrosomal membrane and nucleus exposed. These changes result in release of acrosin enzyme needed for penetration of zona pellucida & hyaluronidase enzyme that causes separation of corona radiata.

Oocyte penetration The sperm must penetrate the corona radiate & zona pellucida. This is aided by acrosomal enzymes, hyalurinodase & protease. Only one sperm penetrates and activates the oocyte and block further sperm penetration. Within the ovum’cytoplasm, the tail of the sperm degenerates & its head enlarges to form the male pronucleus. On penetration of one sperm head, structural changes in membrane of ovum provide further protection against penetration by more sperms (polyspermy). A few hours after sperm penetration, the oocyte divide and a second polar body is expelled thus forming the mature ovum (23 unpaired chromosomes), when the ovum combines with a sperm that carries Y chromosomes (XY) a male fetus is formed. The fertilized ovum undergoes a process of rapid cellular multiplication as it travels along fallopian tube to form blastomere, then morula. When it reaches uterine cavity (after 3-4 days), blastocyst is formed and is implanted in the endometrium (5th -7th day). The trophoblast cells of the blastocyst secrete an LH like hormone called human chorionic gonadotropin (HCG), which acts on the corpus luteum and stimulates it to continue to produce progesterone and estrogen.

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Q. Discuss different Functions of placenta I- Transfer function 1- Diffusion of O2 & CO2 across the placental membrane. 2- Diffusion of food stuffs from mother’s blood into fetal blood. Glucose diffuses down a concentration gradient by facilitated diffusion, protein molecules cannot normally pass however, immunoglobulins can pass. 3- Diffusion of excretory products as urea from fetus back to mother. II- The Protective function: 1- It acts as a barrier against invasion of harmful substances to fetus. 2- It permits passage of IgG. III- Endocrine function A- Human chorionic gonadotropin The secretion from trophoblast cells starts 8 days after ovulation, reaches maximum 10 weeks after ovulation, and then declines to low level until end of pregnancy. Its structure & functions are similar to LH. Functions are:- 1- Prevention of normal involution of corpus luteum. 2- It causes corpus luteum to grow and secrete estrogen & progesterone which cause endometrium to continue growing & store large amounts of nutrients. After 12 weeks, corpus luteum involutes and placenta takes its function. 3- It causes fetal testis to secrete testosterone which stimulate development of male sex organs and descent of testes. 4- HCG stimulates chemoreceptor trigger zone in the vomiting centre so may responsible for morning vomiting in early pregnancy.

Detection of urine or blood HCG is the basis of pregnancy test B- Estrogen Estriol is secreted from placenta to reach maximum toward the end of pregnancy. The precursors are from fetal adrenal that are converted by trophoblasts into estrogens (foetoplacental unit) which have several functions:- 1- They promote growth & enlargement of uterus to accommodate the fetus. 2- Increase the number of oxytocin receptors helping in expulsion of foetus. 2- They promote growth of breast ductal system. 3- Growth & enlargement of mother’s external genitalia. 4- Relaxation of pelvic ligaments & joints to help passage of fetus through pelvis during labour. C- Progesterone It is secreted by corpus luteum in early pregnancy, then by placenta starting from 8th week onward. It reaches a peak value at the end of pregnancy. 1-Progesterone increases endometrial nutrient stores for fetal nourishment. 2- It decreases uterine contractility thus prevents spontaneous abortion. 3- It prepares the breast for lactation by enhancing the development of acini (alveoli). 4- It may produce immunosuppressive effect at the site of implantation preventing foetal rejection. D- Human chorionic somatommamotropin (human placental lactogen) Secreted by placenta at 5th week. Functions are:- 1- It causes partial development of breast. 2- It has protein anabolic action similar to GH. 3- It has lactogenic activity like prolactin.

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4- It decreases glucose utilization by mother by decreasing insulin sensitivity 5- It promotes release of FFA from fat stores of mother. 5- Relaxin Secreted by corpus luteum & placenta. It relaxes symphysis pubis & pelvic ligaments and softens the cervix so facilitating delivery.

N.B. In male, relaxin help to maintain sperm motility & aids in sperm penetration of the ovum. 6. Inhibin from the ovaries: inhibits secretion of FSH.

Q. Describe hormonal regulation of Parturition It means the process by which the baby is born. At termination of pregnancy, uterus becomes more excitable until it begins rhythmic contraction that expels the baby. The causes that lead to parturition are:- I- Hormonal factors that increase uterine contraction

A- Increase estrogen/progesterone ratio From 7th weeks onward estrogen secretion continues to increase, while progesterone secretion remains constant. The increase E/P ratio toward the end of pregnancy is responsible for increase uterine contractility. B- Increase rate of oxytocin secretion by neurogenic reflex to posterior pituitary initiated by stretching of uterine cervix. 1- It stimulates prostaglandins secretion from decidual cells. 2- It produces strong uterine contractions. C- Prostaglandins are found in high concentration during labour. They increase Ca++ within myometrial cells and triggers uterine contraction. 1- They stimulate uterine contractions. 2- They increase the action of oxytocin on uterine muscles. 3-They stimulate synthesis of enzymes that break collagen fibers and soften the cervix.

II- Mechanical factors 1- Stretch of uterine musculature that increases contractility. 2- Stretch of cervix that causes transmission of A.P from cervix to uterus. Uterine involution: Caused by decreased level of estrogen & progesterone. Suckling induces oxytocin release that promote uterine contraction and enhances uterine involution.

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Q. Discuss Physiology of lactation I- Development of mammary glands:- * At puberty, mammary glands develop mainly by effect of : - 1- Estrogen, it causes proliferation of the ducts & deposition of fat. 2- Progesterone, it causes growth of lobule & alveoli. Other hormones are GH, insulin, prolactin, TH & adrenal glucocorticoids. * During pregnancy, full development of breast occurs by the effect of high level of estrogen & progesterone, hCS as well as insulin, GH, prolactin. II- Milk formation (secretion) is stimulated by lactogenic hormones:- * Prolactin 1- It is the hormone responsible for milk formation. Its level increases steadily during pregnancy because estrogen stimulates its secretion. 2- Prolactin and estrogen together stimulate breast growth but lactation does not occur because estrogen antagonizes the milk producing effect of prolactin on the breast. III- Milk ejection (let down):- Stimulated by oxytocin which is released by suckling. The binding of oxytocin to the receptors of the myoepithelial cells surrounding the glands causes them to contract and expel milk from the nipples (of both breasts). The positive feedback cycle ends when the baby stops suckling and removes its mouth from the nipple. Initiation of lactation During pregnancy, very little milk is produced due to high level of estrogen & progesterone which inhibit the action of lactogenic hormones. Milk production in large amounts takes 2-3 days after delivery due to sudden loss of E & P secretion by placenta. This allows prolactin to promote milk secretion instead of colostrums that is secreted before parturition.

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Effect of lactation on ovarian cycle During breast feeding, menstrual cycle usually stops or become irregular. Even if menstruation occurs, cycles are anovulatory. This is due to inhibitory effect of prolactin on GnRH release. Prolactin also decreases effect of LH & FSH on ovaries. Therefore prolonged breast feeding can be used for spacing of pregnancy. Human milk is the most suitable food for infant nutrition as itcontains T &B lymphocytes, macrophages, WBCs, antibacterial & antiviral substances ( IgA, Lysozymes). Composition of milk Colostrum: It is a yellowish secretion produced by the breast in the 1st few days after birth. It contains more immunoglobulins and proteins. Milk contains: 1- Nutrients: water, proteins, fats, and lactose. 2- Many growth factors and hormones that help in tissue development and maturation. 3- Neuropeptides and opioids that shape the infant’s behavior and brain. Advantages of Breast feeding:

For the mother For the baby - Help in uterine involution. - It prevents pregnancy.

- Suitable for digestive system. - provides early protection against infection. - may stimulate development of the baby immune system.